To investigate the effect and mechanism of miR-223 in regulating breast cancer cells and osteoclast in bone metastasis microenvironment.

The role of miR-223 in regulating bone resorption was evaluated by micro-CT and histologic section in miR-223 knockout and C57BL/6 mice. The effect and mechanism of miR-223 in RANKL induced osteoclast formation was investigated. The role and mechanism of miR-223 in regulating breast cancer cell proliferation and apoptosis were investigated in MDA-MB-231 cell line.

The osteoclastic resorption was more severe inmiR-223 knockout mice. In vitro, miR-223 could suppress RANKL activating osteocalst formation by targeting NFIA protein. Besides, overexpression of miR-223 inhibited MDA-MB-231 cell proliferation and promoted its apoptosis by targeting IGF-1R and PI3K/Akt pathway.

miR-223 is a protective factor in bone metastasis microenvironment, which can suppress bone resorption by inhibiting osteoclast formation, and suppress breast cancer cell proliferation, enhance breast cancer cell apoptosis.

To investigate the expression of vascular endothelial growth factor C (VEGF-C), platelet-derived growth factor (PDGF)-AA and PDGF-BB in rectal cancer tissues and their relationship with lymphangiogenesis and lymph node metastasis.

The expression of VEGF-C, PDGF-AA and PDGF-BB in 60 cases of rectal cancer (the rectal cancer group) and 30 cases of normal tissues (the control group) were detected by immunohistochemical staining (SP method). The microlymphatics density (LMVD) in rectal cancer was measured by D2-40, and the correlated analysis was conducted.

The positive expression rates of VEGF-C, PDGF-AA and PDGF-BB in the rectal cancer tissues were significantly higher than those in control group (VEGF-C: 63.3% vs 3.3%, P<0.05; PDGF-AA: 40.0% vs 13.3%, P<0.05; PDGF-BB: 55.0% vs 6.7%, P<0.05). The positive rates of VEGF-C and PDGF-BB in lymph node positive group were significantly higher than those in lymph node negative group (VEGF-C: 86.4% vs 50.0%, P<0.01; PDGF-BB: 77.3% vs 42.1%, P<0.05), but there was no evidence show that PDGF-AA was correlated with lymph node metastasis (54.5% vs 31.6%, P>0.05). LMVD in the lymph node positive group was significantly higher than that in the lymph node negative group [(13.11±2.01) /mm² vs (8.13±2.99) /mm², P<0.05], LMVD in VEGF-C, PDGF-AAand PDGF-BB positive expression group was significantly higher than that of negative expression group[VEGF-C: (12.06±2.20)/mm² vs (6.32±2.41)/mm², P<0.05; PDGF-AA: (11.89±2.46)/mm² vs(8.67±3.67)/mm², P<0.05; PDGF-BB: (12.19±2.22)/mm² vs (7.33±3.02)/mm², P<0.05 ]. The expression of VEGF-C, PDGF-AA and PDGF-BB in rectal cancer was significantly correlated (VEGF-C vs PDGF-AA: r_s=0.366, P<0.05; VEGF-C vs PDGF-BB: r_s=0.650, P<0.05; PDGF-AA vs PDGF-BB: r_s=0.320, P<0.05).

Lymphangiogenesis is one of the important reasons for lymph node metastasis of rectal cancer. VEGF-C, PDGF-AA and PDGF-BB all can promote lymph node metastasis by participating in lymphangiogenesis of rectal cancer, and they may have a certain synergistic effect. Combined medication for VEGF-C, PDGF-AA and PDGF-BB may be more conducive to the prevention and treatment of lymph node metastasis of rectal cancer.